Fig. 1: A detailed roadmap of pig pancreas organogenesis.
From: A multimodal cross-species comparison of pancreas development
a Schematic comparison of pancreas organogenesis in mouse, pig and human1,6,7. Pancreas organogenesis initiates when the pancreatic buds (dorsal bud shown) emerge from the foregut endoderm while predicted multipotent pancreatic progenitor cells (MPC) expand into a multi-layer epithelium (T1). In mouse and pig but not human, neurogenin 3-induced endocrinogenesis marks the primary (1°) transition, generating alpha cells and few beta cells. Pancreatic morphogenesis (T2) occurs after the fusion of the pancreatic buds. The epithelium undergoes polarization, microlumen formation and coalescence into the near single-layer epithelial tree, which is subsequently patterned into trunk and tip domains during branching morphogenesis. This coincides with progenitor differentiation forming exocrine and endocrine compartments, referred to as secondary (2°) transition when the bulk of beta cells emerge. During T3, the pancreatic ductal and acinar cells proliferate and terminally differentiate, while delaminating endocrine cells form proto-islets of various sizes. b–g Bright-field images of wild-type pig embryos or embryonic pancreas (scale bar 2 mm) and immunofluorescence identification of lineage markers highlighting differentiation events in tissue sections (scale bar 50 µm) at different time points. Images are representative of 3 samples per time point. h Schematic comparison of mouse and pig development speeds relative to human, showing the timing of each pancreas developmental milestone (labeled in a) as a percentage of gestation duration marked with dashed lines. i Uniform Manifold Approximation Projection (UMAP) plots showing integrated pig pancreas atlas and cluster changes from E22-85. Cells at each developmental stage (see b-g) are highlighted and colored by cell type, with a pie chart of relative cell type composition at the upper right corner. j Dot plot showing mean gene expression of marker genes for each cluster of the integrated pig pancreas atlas. i and j: scRNA-seq of pancreatic cells from wild-type and INS-eGFP pigs. Detailed sample information is provided in Supplementary Data 1.
